The present study aimed to identify some of the mechanisms affecting spinal compressive loadbearing capacity in neutral postures. Two spinal geometries were employed in the evaluation of the stabilizing mechanisms of the spine in standing neutral postures. Large-displacement finite-element models were used for parametric studies of the effect of load distribution, initial geometry, and pelvic rotation on the compression stability of the spine. The role of muscles in stabilization of the spine was also investigated using a unique muscle model based on kinematic conditions. The model with a realistic load configuration supported the largest compression load. The compressive load-bearing capacity of the passive thoracolumbar spine was found to be significantly enhanced by pelvic rotation and minimal muscular forces. Pelvic rotation and muscle forces were sensitive to the initial positioning of T1 and the spinal curvatures. To sustain the physiological gravity load, the lordotic angle increased as observed in standing postures. These predictions are in good agreement with in vitro and in vivo observations. The load-bearing potential of the ligamentous spine in compression is substantially increased by controlling its deformation modes through minimal exertion of selected muscles and rotation of the pelvis.
IntroductionAn understanding of mechanisms for the load-resisting capacity of the human spine and load sharing between the passive ligamentous spine and the active muscle tissues in neutral posture is essential for investigation of spinal functioning in normal and pathologic conditions. Several approaches have been taken in previous numerical models for static analysis of the lumbar spine: maximum moment-generating capacity models [7,38], transverse section equilibrium models [36], and stability criterion models [5,10,16]. Experimental measurements of, for instance, electromyographic activities in spinal muscles and Abstract The neutral position of the spine is the posture most commonly sustained throughout daily activities. Previous investigations of the spine focused mainly on maximal exertions in various symmetric and asymmetric postures. This report proposes a new synergetic approach for analysis of the spine in neutral postures and evaluates its performance. The model consists of passive components, the osteoligamentous spine, and active components, the spinal muscles. The muscle architecture includes 60 muscles inserting onto both the rib cage and lumbar vertebral bodies. The passive spine is simulated by a finite element model, while kinematic constraints and optimization are used for resolution of a redundant muscle recruitment problem. Although the passive spine alone exhibits little resistance to a vertical load, its load-bearing capacity in neutral posture is significantly enhanced by the muscles, i.e., the passive spine and its muscles must be considered as a synergetic system. The proposed method is used to investigate the response of the spine when the T1 vertebra displaces 40 mm anteriorly and 20 mm posteriorly from its initial position. The sacrum is fixed at all times and the T1 displacements are achieved by the action of muscles. The results suggest that relatively small muscle activations are sufficient to stabilize the spine in neutral posture under the body weight. The results also indicate that muscles attaching onto the rib cage are important for control of the overall spinal posture and maintenance of equilibrium. The muscles inserting onto the lumbar vertebrae are found mainly to enhance the stability of the spine. The proposed method also predicts forces and moments carried by the passive system. Flexion moments ranging from 8000 Nmm to 15,000 Nmm, corresponding to decreases in lordosis of 6°and 7.5°respectively, are found to be carried by the passive spine at the thoracolumbar junction when the T1 vertebra is 40 mm anterior to its initial position.
Cystic fibrosis patients suffer from a progressive, often fatal lung disease, which is based on a complex interplay between chronic infections, locally accumulating immune cells and pulmonary tissue remodeling. Although group-2 innate lymphoid cells (ILC2s) act as crucial initiators of lung inflammation, our understanding of their involvement in the pathogenesis of cystic fibrosis remains incomplete. Here we report a marked decrease of circulating CCR6 + ILC2s in the blood of cystic fibrosis patients, which significantly correlated with high disease severity and advanced pulmonary failure, strongly implicating increased ILC2 homing from the peripheral blood to the chronically inflamed lung tissue in cystic fibrosis patients. On a functional level, the CCR6 ligand CCL20 was identified as potent promoter of lung-directed ILC2 migration upon inflammatory conditions in vitro and in vivo using a new humanized mouse model with light-sheet fluorescence microscopic visualization of lung-accumulated human ILC2s. In the lung, blood-derived human ILC2s were able to augment local eosinophil and neutrophil accumulation and induced a marked upregulation of pulmonary type-VI collagen expression. Studies in primary human lung fibroblasts additionally revealed ILC2-derived IL-4 and IL-13 as important mediators of this type-VI collagen-inducing effect. Taken together, the here acquired results suggest that pathologically increased CCL20 levels in cystic fibrosis airways induce CCR6-mediated lung homing of circulating human ILC2s. Subsequent ILC2 activation then triggers local production of type-VI collagen and might thereby drive extracellular matrix remodeling potentially influencing pulmonary tissue destruction in cystic fibrosis patients. Thus, modulating the lung homing capacity of circulating ILC2s and their local effector functions opens new therapeutic avenues for cystic fibrosis treatment.
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